Local osmotic gradients drive the water flux associated with Na+/glucose cotransport

It recently was proposed [Loo, D. D. F., Zeuthen, T., Chandy, G. & Wright, E. M. (1996) Proc. Natl. Acad. Sci. USA 93, 13367–13370] that SGLT1, the high affinity intestinal and renal sodium/glucose cotransporter carries water molecules along with the cosubstrates with a strict stoichiometry of two Na+, one glucose, and ≈220 water molecules per transport cycle. Using electrophysiology together with sensitive volumetric measurements, we investigated the nature of the driving force behind the cotransporter-mediated water flux. The osmotic water permeability of oocytes expressing human SGLT1 (Lp ± SE) averaged 3.8 ± 0.3 × 10−4 cm⋅s−1 (n = 15) and addition of 100 μM phlorizin (a specific SGLT1 inhibitor) reduced the permeability to 2.2 ± 0.2 × 10−4 cm⋅s−1 (n = 15), confirming the presence of a significant water permeability closely associated with the cotransporter. Addition of 5 mM α-methyl-glucose (αMG) induced an average inward current of 800 ± 10 nA at −50 mV and a water influx reaching 120 ± 20 pL cm−2 ⋅s−1 within 5–8 min. After rapidly inhibiting the Na+/glucose cotransport with phlorizin, the water flux remained significantly elevated, clearly indicating the presence of a local osmotic gradient (Δπ) estimated at 16 ± 2 mOsm. In short-term experiments, a rapid depolarization from −100 to 0 mV in the presence of αMG decreased the cotransport current by 94% but failed to produce a comparable reduction in the swelling rate. A mathematical model depicting the intracellular accumulation of transported osmolytes can accurately account for these observations. It is concluded that, in SGLT1-expressing oocytes, αMG-dependent water influx is induced by a local osmotic gradient by using both endogenous and SGLT1-dependent water permeability.

IL-4 determines eicosanoid formation in dendritic cells by down-regulation of 5-lipoxygenase and up-regulation of 15-lipoxygenase 1 expression

Dendritic cell (DC) differentiation from human CD34+ hematopoietic progenitor cells (HPCs) can be triggered in vitro by a combination of cytokines consisting of stem cell factor, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α. The immune response regulatory cytokines, IL-4 and IL-13, promote DC maturation from HPCs, induce monocyte-DC transdifferentiation, and selectively up-regulate 15-lipoxygenase 1 (15-LO-1) in blood monocytes. To gain more insight into cytokine-regulated eicosanoid production in DCs we studied the effects of IL-4/IL-13 on LO expression during DC differentiation. In the absence of IL-4, DCs that had been generated from CD34+ HPCs in response to stem cell factor/granulocyte-macrophage colonystimulating factor/tumor necrosis factor α expressed high levels of 5-LO and 5-LO activating protein. However, a small subpopulation of eosinophil peroxidase+ (EOS-PX) cells significantly expressed 15-LO-1. Addition of IL-4 to differentiating DCs led to a marked and selective down-regulation of 5-LO but not of 5-LO activating protein in DCs and in EOS-PX+ cells and, when added at the onset of DC differentiation, also prevented 5-LO up-regulation. Similar effects were observed during IL-4- or IL-13-dependent monocyte-DC transdifferentiation. Down-regulation of 5-LO was accompanied by up-regulation of 15-LO-1, yielding 15-LO-1+ 5-LO-deficient DCs. However, transforming growth factor β1 counteracted the IL-4-dependent inhibition of 5-LO but only minimally affected 15-LO-1 up-regulation. Thus, transforming growth factor β1 plus IL-4 yielded large mature DCs that coexpress both LOs. Localization of 5-LO in the nucleus and of 15-LO-1 in the cytosol was maintained at all cytokine combinations in all DC phenotypes and in EOS-PX+ cells. In the absence of IL-4, major eicosanoids of CD34+-derived DCs were 5S-hydroxyeicosatetraenoic acid (5S-HETE) and leukotriene B4, whereas the major eicosanoids of IL-4-treated DCs were 15S-HETE and 5S-15S-diHETE. These actions of IL-4/IL-13 reveal a paradigm of eicosanoid formation consisting of the inhibition of one and the stimulation of another LO in a single leukocyte lineage.

Pràctica 1: Aspectes del desenvolupament evolutiu en la legislació

Aquesta pràctica pretén que l’alumnat tinga un acostament al decret que estableix el currículum del segon cicle d’Educació Infantil a la Comunitat Valenciana des de l’enfocament de la psicologia evolutiva. S’analitzaran els aspectes principals del desenvolupament: físic, cognitiu, afectiu, social i moral que apareixen en el decret i la importància que tenen per a l’evolució del xiquet o xiqueta. De la mateixa manera, s’estudiaran les variables contextuals (família, escola, entorn pròxim, etc.) que influeixen en aquest desenvolupament.

Distribution of clay minerals in surface sediments of the Eurasian Arctic Ocean

Clay-mineral distributions in the Arctic Ocean and the adjacent Eurasian shelf areas are discussed to identify source areas and transport pathways of terrigenous material in the Arctic Ocean. The main clay minerals in Eurasian Arctic Ocean sediments are illite and chlorite. Smectite and kaolinite occur in minor amounts in these sediments, but show strong variations in the shelf areas. These two minerals are therefore reliable in reconstructions of source areas of sediments from the Eurasian Arctic. The Kara Sea and the western part of the Laptev Sea are enriched in smectite, with highest values of up to 70% in the deltas of the Ob and Yenisey rivers. Illite is the dominant clay mineral in all the investigated sediments except for parts of the Kara Sea. The highest concentrations with more than 70% illite occur in the East Siberian Sea and around Svalbard. Chlorite represents the clay mineral with lowest concentration changes in the Eastern Arctic, ranging between 10 and 25%. The main source areas for kaolinite in the Eurasian Arctic are Mesozoic sedimentary rocks on Franz-Josef Land islands. Based on clay-mineral data, transport of the clay fraction via sea ice is of minor importance for the modern sedimentary budget in the Arctic basins.

Data compilation of ESOP

The work in this sub-project of ESOP focuses on the advective and convective transforma-tion of water masses in the Greenland Sea and its neighbouring areas. It includes observational work on the sub-mesoscale and analysis of hydrographic data up to the gyre-scale. Observations of active convective plumes were made with a towed chain equipped with up to 80 CTD sensors, giving a horizontal and vertical resolution of the hydrographic fields of a few metres. The observed scales of the penetrative convective plumes compare well with those given by theory. On the mesoscale the structure of homogeneous eddies formed as a result of deep convection was observed and the associated mixing and renewal of the intermediate layers quantified. The relative importance and efficiency of thermal and haline penetrative convection in relation to the surface boundary conditions (heat and salt fluxes and ice cover) and the ambient stratification are studied using the multi year time series of hydro-graphic data in the central Greenland Sea. The modification of the water column of the Greenland Sea gyre through advection from and mixing with water at its rim is assessed on longer time scales. The relative contributions are quantified using modern water mass analysis methods based on inverse techniques. Likewise the convective renewal and the spreading of the Arctic Intermediate Water from its formation area is quantified. The aim is to budget the heat and salt content of the water column, in particular of the low salinity surface layer, and to relate its seasonal and interannual variability to the lateral fluxes and the fluxes at the air-sea-ice interface. This will allow to estimate residence times for the different layers of the Greenland Sea gyre, a quantity important for the description of the Polar Ocean carbon cycle.

Consolidation characteristics of outer Bengal Fan deposits (Table 1)

The state of consolidation of outer Bengal Fan deposits is closely related to their depositional history. Early Pleistocene sediments are underconsolidated, i.e., fabric strength is lower than under equilibrium with the present overburden stress, at depths greater than 60-80 mbsf. This may be due to rapid accumulation (>15-20 cm/k.y.) and overlying low-permeability (<10**-7 cm/s) deposits. The underlying Pliocene sediments are overconsolidated, i.e., fabric strength is higher than in equilibrium with the present overburden stress; at Sites 717 and 719 the sediments are slightly overconsolidated, whereas at Site 718 the overconsolidation is significant. Overconsolidation is explained by erosion that occurred during the early Pleistocene for which a stratigraphic gap was recorded in the drilled cores. The eroded section is estimated to be in the range of 10-40 m at Sites 717 and 719, respectively, and 130-150 m at Site 718. Below 250-300 mbsf the most sediments are normally consolidated. The amount of erosion seems to be related to block rotation and uplift due to intraplate deformation.

Automobile marketing practices : hearings, Eighty-fourth Congress, second session pursuant to S. Res. 13 continued by S. Res. 163... January 19,20,23, and February 21,22,23,29, March 1,6,7,8,9,10, 1956.

pt. 1. January 19, 20, 23, February 21-23, 29, March 1, 6-10, 1956. 1225 p.--pt. 2. June 4-6, 12, 21, 1956. pp. 1227-1533.

Na 1 Nachlass Max Horkheimer, 802 - "Dialektik der Aufklärung" von Max Horkheimer und Theodor W. Adorno (p. XI 6.3 - XI 6.42)

3. Aus der "Dialektik der Aufklärung"; Kapitel: "Juliette oder Aufklärung und Moral". Typoskript mit dem Titel "Aufklärung und Rigorismus", mit handschriftlichen Korrekturen, 52 Blatt (2 Exemplare); 4. Aus der "Dialektik der Aufklärung"; Kapitel: "Kulturindustrie". Typoskript mit dem Titel "Das Schema der Massenkultur":; 4a) Typoskript mit handschriftlichen Korrekturen, 67 Blatt; 4b) Typoskript mit eigenen Korrekturen, 106 Blatt; 5. - 110. Gedruckte und ungedruckte Aufzeichnungen und Entwürfe zur "Dialektik der Aufklärung: Sammlungen A, B, C, D, die teilweise identisch sind; 5. - 42. Sammlung A: "Aphorismen"; 5. "Zum Problem der Bedürfnisse". Typoskript, 5 Blatt; 6. "Mensch und Tier". Typoskript mit eigenen Korrekturen, 12 Blatt; 7. "Propaganda". Typoskript, 2 Blatt; 8. "Straftheorie". Typoskript mit eigenen Korrekturen, 3 Blatt; 9. "Dichtung und Moral". Typoskript mit eigenen Korrekturen, 5 Blatt; 10. "Zur Genese der Dummheit". Typoskript, 3 Blatt; 11. "Interesse am Körper". Typoskript mit eigenen Korrekturen, 6 Blatt; 12. "Philosophie und Arbeitsteilung". Typoskript, 3 Blatt; 13. "Widersprüche". Typoskript, 4 Blatt; 14. "Geschichte der amerikanischen Arbeiterschaft". Typoskript, 1 Blatt; 15. "Feind". Typoskript, 2 Blatt; 16. "Gezeichnet". Typoskript mit eigenen Korrekturen, 2 Blatt; 17. "Erkenntnis und Sprache". Typoskript, 1 Blatt; 18. "Unmöglichkeit der Dichtung". Typoskript, 1 Blatt; 19. "Erbsünde und Kopula". Typoskript, 2 Blatt; 20. "Die Einseitigkeit der Negativität". Typoskript, 2 Blatt [= "Für Voltaire" in der "Dialektik der Aufklärung"]; 21. "Klassifikation". Typoskript mit eigenen Ergänzungen, 1 Blatt; 22. "Jüdischer Charakter". Typoskript mit eigenen Korrekturen, 1 Blatt; 23. "Lawine". Typoskript mit eigenen Korrekturen, 2 Blatt; 24. "Solidarität". Typoskript mit eigenen Korrekturen, 2 Blatt; 25. "Bewußtsein". Typoskript, 1 Blatt; 26. "Gegen Bescheidwissen". Typoskript, 1 Blatt; 27. "Der Gedanke". Typoskript, 1 Blatt; 28. "Quand-même". Typoskript, 2 Blatt; 29. "Leeres Erschrecken". Typoskript mit eigenen Korrekturen, 2 Blatt; 30. "Haupt- und Nebensatz". Typoskript, 3 Blatt; 31. "Verwandlung der Idee in Herrschaft". Typoskript mit eigenen Korrekturen, 5 Blatt; 32. "Isolierung durch Verkehr". Typoskript, 1 Blatt; 33. "Kampf und Gewaltlosigkeit". Typoskript, 6 Blatt; 34. "Zwei Welten". Typoskript, 2 Blatt; 35. "Zur Theorie der Gespenster". Typoskript, 1 Blatt; 36. "Notiz" [= "Umschlag der idealistischen Dialektik"]. Typoskript, 1 Blatt; 37. "Massengesellschaft". Typoskript, 1 Blatt; 38. "Tierpsychologie". Typoskript, 1 Blatt; 39. "Denkmale der Humanität". Typoskript mit eigenen Korrekturen, 1 Blatt; 40. "Physiognomik". Typoskript mit eigenen Korrekturen, 1 Blatt; 41. "Die Rackets und der Geist". Typoskript mit eigenen Korrekturen, 7 Blatt; 42. "Altmodisches Problem". Typoskript mit eigenen Korrekturen, 2 Blatt;

Becoming pregnant: exploring the perspectives of women living with diabetes

Background The risk of adverse pregnancy outcome for women with type 1 diabetes is reduced through tight diabetes control. Most women enter pregnancy with inadequate blood glucose control. Interview studies with women suggest the concept of ‘planned’ and ‘unplanned’ pregnancies is unhelpful. Aim To explore women's accounts of their journeys to becoming pregnant while living with type 1 diabetes. Design of study Semi-structured interviews with 15 women living with pre-gestational type 1 diabetes, between 20 and 30 weeks gestation and with a normal pregnancy ultrasound scan. Setting Four UK specialist diabetes antenatal clinics. Method Interviews explored women's journeys to becoming pregnant and the impact of health care. Analysis involved comparison of women's accounts of each pregnancy and a thematic analysis. Results Women's experiences of becoming pregnant were diverse. Of the 40 pregnancies described, at least one positive step towards becoming pregnant was taken by 11 women in 23 pregnancies but not in the remaining 17 pregnancies, with variation between pregnancies. Prior to and in early pregnancy, some women described themselves as experts in their diabetes but most described seeking and/or receiving advice from their usual health professionals. Three women described pre-conception counselling and the anxiety this provoked. Conclusion For women living with type 1 diabetes each pregnancy is different. The concept of planned and unplanned pregnancy is unhelpful for designing health care. Formal preconception counselling can have unintended consequences. Those providing usual care to women are well positioned to provide advice and support to women about becoming pregnant, tailoring it to the changing needs and situation of each woman.

Statin use in rheumatoid arthritis in relation to actual cardiovascular risk:evidence for substantial undertreatment of lipid-associated cardiovascular risk?

Background Cardiovascular disease (CVD) is partially attributed to traditional cardiovascular risk factors, which can be identified and managed based on risk stratification algorithms (Framingham Risk Score, National Cholesterol Education Program, Systematic Cardiovascular Risk Evaluation and Reynolds Risk Score). We aimed to (a) identify the proportion of at risk patients with rheumatoid arthritis (RA) requiring statin therapy identified by conventional risk calculators, and (b) assess whether patients at risk were receiving statins. Methods Patients at high CVD risk (excluding patients with established CVD or diabetes) were identified from a cohort of 400 well characterised patients with RA, by applying risk calculators with or without a ×1.5 multiplier in specific patient subgroups. Actual statin use versus numbers eligible for statins was also calculated. Results The percentage of patients identified as being at risk ranged significantly depending on the method, from 1.6% (for 20% threshold global CVD risk) to 15.5% (for CVD and cerebrovascular morbidity and mortality) to 21.8% (for 10% global CVD risk) and 25.9% (for 5% CVD mortality), with the majority of them (58.1% to 94.8%) not receiving statins. The application of a 1.5 multiplier identified 17% to 78% more at risk patients. Conclusions Depending on the risk stratification method, 2% to 26% of patients with RA without CVD have sufficiently high risk to require statin therapy, yet most of them remain untreated. To address this issue, we would recommend annual systematic screening using the nationally applicable risk calculator, combined with regular audit of whether treatment targets have been achieved.

Global compilation of benthic data sets I

Approaches to quantify the organic carbon accumulation on a global scale generally do not consider the small-scale variability of sedimentary and oceanographic boundary conditions along continental margins. In this study, we present a new approach to regionalize the total organic carbon (TOC) content in surface sediments (<5 cm sediment depth). It is based on a compilation of more than 5500 single measurements from various sources. Global TOC distribution was determined by the application of a combined qualitative and quantitative-geostatistical method. Overall, 33 benthic TOC-based provinces were defined and used to process the global distribution pattern of the TOC content in surface sediments in a 1°x1° grid resolution. Regional dependencies of data points within each single province are expressed by modeled semi-variograms. Measured and estimated TOC values show good correlation, emphasizing the reasonable applicability of the method. The accumulation of organic carbon in marine surface sediments is a key parameter in the control of mineralization processes and the material exchange between the sediment and the ocean water. Our approach will help to improve global budgets of nutrient and carbon cycles.

Age models, accumulation rates, and grain size distributions of sediment cores from the northern subtropical Atlantic

The terrigenous sediment proportion of the deep sea sediments from off Northwest Africa has been studied in order to distinguish between the aeolian and the fluvial sediment supply. The present and fossil Saharan dust trajectories were recognized from the distribution patterns of the aeolian sediment. The following timeslices have been investigated: Present, 6,000, 12,000 and 18,000 y. B. P. Furthermore, the quantity of dust deposited off the Saharan coast has been estimated. For this purpose, 80 surface sediment samples and 34 sediment cores have been analysed. The stratigraphy of the cores has been achieved from oxygen isotopic curves, 14C-dating, foraminiferal transfer temperatures, and carbonate contents. Silt sized biogenic opal generally accounts for less than 2 % of the total insoluble sediment proportion. Only under productive upwelling waters and off river mouths, the opal proportion exceeds 2 % significantly. The modern terrigenous sediment from off the Saharan coast is generally characterized by intensely stained quartz grains. They indicate an origin from southern Saharan and Sahelian laterites, and a zonal aeolian transport in midtropospheric levels, between 1.5 an 5.5 km, by 'Harmattan' Winds. The dust particles follow large outbreaks of Saharan air across the African coast between 15° and 21° N. Their trajectories are centered at about 18° N and continue further into a clockwise gyre situated south of the Canary Islands. This course is indicated by a sickle-shaped tongue of coarser grain sizes in the deep-sea sediment. Such loess-sized terrigenous particles only settle within a zone extending to 700 km offshore. Fine silt and clay sized particles, with grain sizes smaller than 10- 15 µm, drift still further west and can be traced up to more than 4,000 km distance from their source areas. Additional terrigenous silt which is poor in stained quartz occurs within a narrow zone off the western Sahara between 20° and 27° N only. It depicts the present dust supply by the trade winds close to the surface. The dust load originates from the northwestern Sahara, the Atlas Mountains and coastal areas, which contain a particularly low amount of stained quartz. The distribution pattern of these pale quartz sediments reveals a SSW-dispersal of dust being consistent with the present trade wind direction from the NNE. In comparison to the sediments from off the Sahara and the deeper subtropical Atlantic, the sediments off river mouths, in particular off the Senegal river, are characterized by an additional input of fine grained terrigenous particles (< 6 µm). This is due to fluvial suspension load. The fluvial discharge leads to a relative excess of fine grained particles and is observed in a correlation diagram of the modal grain sizes of terrigenous silt with the proportion of fine fraction (< 6 µm). The aeolian sediment contribution by the Harmattan Winds strongly decreased during the Climatic Optimum at 6,000 y. B. P. The dust discharge of the trade winds is hardly detectable in the deep-sea sediments. This probably indicates a weakened atmospheric circulation. In contrast, the fluvial sediment supply reached a maximum, and can be traced to beyond Cape Blanc. Thus, the Saharan climate was more humid at 6,000 y B. P. A latitudinal shift of the Harmattan driven dust outbreaks cannot be observed. Also during the Glacial, 18,000 y. B. P., Harmattan dust transport crossed the African coast at latitudes of 15°-20° N. Its sediment load increased intensively, and markedly coarser grains spread further into the Atlantic Ocean. An expanded zone of pale-quart sediments indicates an enhanced dust supply by the trade winds blowing from the NE. No synglacial fluvial sediment contribution can be recognized between 12° and 30° N. This indicates a dry glacial climate and a strengthened stmospheric circulation over the Sahelian and Saharan region. The climatic transition pahes, at 12, 000 y. B. P., between the last Glacial and the Intergalcial, which is compareable to the Alerod in Europe, is characterized by an intermediate supply of terrigenous particles. The Harmattan dust transport wa weaker than during the Glacial. The northeasterly trade winds were still intensive. River supply reached a first postglacial maximum seaward of the Senegal river mouth. This indicates increasing humidity over the southern Sahara and a weaker atmospheric circulation as compared to the glacial. The accumulation rates of the terrigenous silt proportion (> 6 µm) decrcase exponentially with increasing distance from the Saharan coast. Those of the terrigenous fine fraction (< 6 µm) follow the same trend and show almost similar gradients. Accordingly, also the terrigenous fine fraction is believed to result predominantly from aeolian transport. In the Atlantic deep-sea sediments, the annual terrigenous sediment accumulation has fluctuated, from about 60 million tons p. a. during the Late Glacial (13,500-18,000 y. B. P, aeolian supply only) to about 33 million tons p. a. during the Holocene Climatic Optimum (6,000-9,000 y. B. P, mainly fluvial supply), when the river supply has reached a maximum, and to about 45 million tons p. a. during the last 4,000 years B. P. (fluvial supply only south of 18° N).